Analysis of Survival and Response to Lenvatinib in Unresectable Hepatocellular Carcinoma

Abstract

The association between radiological response and overall survival (OS) was retrospectively evaluated in patients treated with lenvatinib as a first-line systemic treatment for unresectable hepatocellular carcinoma. A total of 182 patients with Child-Pugh class A liver function and an Eastern Cooperative Oncology Group performance status of zero or one were enrolled. Radiological evaluation was performed using Response Evaluation Criteria in Solid Tumors (RECIST) and modified Response Evaluation Criteria in Solid Tumors (mRECIST). Initial radiological evaluation confirmed significant stratification of OS by efficacy judgment with both RECIST and mRECIST, and that initial radiological response was an independent prognostic factor for OS on multivariate analysis. Furthermore, in patients with stable disease (SD) at initial evaluation, macrovascular invasion at the initial evaluation on RECIST and modified albumin-bilirubin grade at initial evaluation on mRECIST were independent predictors of OS on multivariate analysis. In conclusion, if objective response is obtained at the initial evaluation, continuation of treatment appears desirable because prolonged OS can be expected; but, if SD is obtained at the initial evaluation, one should determine whether to continue or switch to the next treatment, with careful consideration of factors related to the tumor and hepatic reserve at the initial evaluation.

Keywords: Response Evaluation Criteria in Solid Tumors (RECIST); hepatocellular carcinoma; lenvatinib; modified Response Evaluation Criteria in Solid Tumors (mRECIST); molecular targeted agent; overall survival; radiological response; sequential therapy.

Figure 1

Overall survival (OS) and progression-free survival (PFS) from the initiation of lenvatinib in the 182 patients included in this study. (a) OS from the initiation of lenvatinib. (b) PFS from the initiation of lenvatinib.

Figure 2

Comparison of overall survival (OS) by response at the first, second, and best responses evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) and modified Response Evaluation Criteria in Solid Tumors (mRECIST). (a) OS at the best response evaluated by mRECIST (OR 25.4 months, SD 17.9 months, PD 9.1 months, p < 0.005). (b) OS at the first response evaluated by mRECIST (OR 32.1 months, SD 19.3 months, PD 9.1 months, p < 0.005). (c) OS at the second response evaluated by mRECIST (OR 32.1 months, SD 21.4 months, PD 17.9 months, p < 0.005). (d) OS at the best response evaluated by RECIST (OR 30.2 months, SD 20.4 months, PD 9.1 months, p < 0.005). (e) OS at the first response evaluated by RECIST (OR not reached, SD 25.4 months, PD 9.1 months, p < 0.005). (f) OS at the second response evaluated by RECIST (OR not reached, SD 21.6 months, PD 18.7 months, p = 0.006).

Figure 3

Comparison of overall survival (OS) from the initial objective evaluation of lenvatinib in patients with SD at the initial radiological response evaluation. (a) OS from the initial objective evaluation by RECIST with or without macroscopic vascular invasion (absent 28.8 months, present 9.7 months, p < 0.005). (b) OS from the initial objective evaluation by mRECIST by mALBI grade (mALBI 1–2a 24.4 months, mALBI 2b 10.6 months, p = 0.009).